ABSTRACT An estimated 2.5 million people worldwide are challenged with managing the disfiguring, debilitating, and often unremitting symptoms of systemic sclerosis (SSc; scleroderma). SSc is a rare, chronic multisystem autoimmune disease that often leads to high levels of pain, fatigue, sleep disturbance, and altered mood (i.e., anxiety and depressive symptoms) as well as significant functional disability. Prior research in SSc has focused on single symptoms and their effects on patient outcomes. However, little is known about the prevalence and impact of multiple co-occurring symptoms, or symptom clusters, and their relationship with functional disability in patients with SSc. The purpose of this study is to understand the distinct symptom experiences of SSc patients with co-occurring symptoms and their relationship with functional disability to inform future development of targeted symptom management interventions. This study aims to: 1) identify subgroups of SSc patients with distinct symptom experiences using a prespecified symptom cluster (i.e., pain, fatigue, sleep disturbance, and altered mood); 2) determine the individual characteristics (i.e., demographic and clinical characteristics) associated with each symptom cluster subgroup; and, 3) determine the extent to which symptom cluster subgroups predict functional disability. This descriptive cross-sectional study will use existing symptom data collected at enrollment from the Scleroderma Patient-centered Intervention Network (SPIN) Cohort (N=1942), including the Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29) and the Health Assessment Questionnaire Disability Index (HAQ-DI). Latent profile analysis (LPA) will be used to identify subgroups of SSc patients with distinct symptom profiles using a prespecified symptom cluster. Bivariate and multiple regression models will be used to determine individual characteristics associated with each symptom cluster subgroup. Finally, a regression model approach will be used to determine whether subgroup membership is associated with functional disability. The proposed study supports the National Institute of Nursing Research?s mission and area of strategic focus in symptom science by providing a new lens to SSc symptom research to capture the complexities of the symptom experience through exploration of multiple co-occurring symptoms, or symptom clusters, and their effects on functional disability in SSc. Findings from this study will inform the next stages of symptom science research (i.e., biomarker discovery and clinical application) in patients with SSc and has the strong potential to inform symptom science in other rare diseases.